PROJECT SUMMARY: Staphylococcus aureus (SA), including methicillin-resistant (MRSA), is the most common cause of skin and soft tissue infection (SSTI) in the US. To date, no vaccine to prevent SA infection has succeeded in human trials. Meanwhile, the need for a vaccine continues to escalate as does the ability of this pathogen to acquire antibiotic resistance. Our goal is to demonstrate the effectiveness of virus-like particles (VLPs) as an innovative platform to induce immune control of bacterial virulence regulation. VLPs are a novel approach to the design of vaccines targeting bacterial infection and the ability of VLP-based vaccines targeting SA virulence regulation has not been investigated. Therefore, the goal of this proposal is to test the hypothesis that presentation of SA virulence regulating peptides on VLPs can be used to induce protective immunity. Importantly, unlike other platforms and experimental adjuvants, VLPs are currently used in FDA- approved vaccines (like the current HPV vaccines). Therefore, if experimental approaches using VLPs are successful in animal models, they can potentially translate into human trials fairly readily.